IE843002L - Betamethasone dipropionate cream - Google Patents
Betamethasone dipropionate creamInfo
- Publication number
- IE843002L IE843002L IE843002A IE300284A IE843002L IE 843002 L IE843002 L IE 843002L IE 843002 A IE843002 A IE 843002A IE 300284 A IE300284 A IE 300284A IE 843002 L IE843002 L IE 843002L
- Authority
- IE
- Ireland
- Prior art keywords
- percent
- composition
- water
- betamethasone dipropionate
- white
- Prior art date
Links
- 229960001102 betamethasone dipropionate Drugs 0.000 title claims abstract description 22
- CIWBQSYVNNPZIQ-XYWKZLDCSA-N betamethasone dipropionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CIWBQSYVNNPZIQ-XYWKZLDCSA-N 0.000 title claims abstract description 22
- 239000006071 cream Substances 0.000 title description 9
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 206010061218 Inflammation Diseases 0.000 claims abstract description 3
- 230000004054 inflammatory process Effects 0.000 claims abstract description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 235000019271 petrolatum Nutrition 0.000 claims description 18
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 claims description 15
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 14
- 239000000600 sorbitol Substances 0.000 claims description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 13
- 239000003995 emulsifying agent Substances 0.000 claims description 12
- 239000003871 white petrolatum Substances 0.000 claims description 12
- 229940045860 white wax Drugs 0.000 claims description 12
- XMSXQFUHVRWGNA-UHFFFAOYSA-N Decamethylcyclopentasiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1 XMSXQFUHVRWGNA-UHFFFAOYSA-N 0.000 claims description 11
- 229940086555 cyclomethicone Drugs 0.000 claims description 11
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 claims description 10
- 229940056318 ceteth-20 Drugs 0.000 claims description 10
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 claims description 8
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
- 239000000839 emulsion Substances 0.000 claims description 7
- 239000004264 Petrolatum Substances 0.000 claims description 6
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 claims description 6
- 229940066842 petrolatum Drugs 0.000 claims description 6
- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 claims description 5
- 235000013871 bee wax Nutrition 0.000 claims description 4
- 239000012166 beeswax Substances 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 claims description 3
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 3
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 3
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 3
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 claims description 3
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 claims description 3
- 229940113124 polysorbate 60 Drugs 0.000 claims description 3
- 230000002335 preservative effect Effects 0.000 claims description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 3
- 229960005078 sorbitan sesquioleate Drugs 0.000 claims description 3
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 claims description 2
- 230000015556 catabolic process Effects 0.000 claims description 2
- 229960002303 citric acid monohydrate Drugs 0.000 claims description 2
- 238000006731 degradation reaction Methods 0.000 claims description 2
- 244000005700 microbiome Species 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- FSVRFCBLVIJHQY-UHFFFAOYSA-N 2-[2-(2-hexadecoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCO FSVRFCBLVIJHQY-UHFFFAOYSA-N 0.000 claims 3
- 239000007762 w/o emulsion Substances 0.000 abstract description 3
- 229940100611 topical cream Drugs 0.000 abstract 1
- 239000002674 ointment Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 5
- 238000013019 agitation Methods 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 2
- TWHXWYVOWJCXSI-UHFFFAOYSA-N phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O TWHXWYVOWJCXSI-UHFFFAOYSA-N 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FKOKUHFZNIUSLW-UHFFFAOYSA-N 2-Hydroxypropyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(C)O FKOKUHFZNIUSLW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- JYUISUQASVVQPI-UHFFFAOYSA-K O.O.O.[Na+].[Na+].[Na+].CC(O)CO.CC1=CC(O)=CC=C1Cl.OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O Chemical compound O.O.O.[Na+].[Na+].[Na+].CC(O)CO.CC1=CC(O)=CC=C1Cl.OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O JYUISUQASVVQPI-UHFFFAOYSA-K 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- IJCWFDPJFXGQBN-RYNSOKOISA-N [(2R)-2-[(2R,3R,4S)-4-hydroxy-3-octadecanoyloxyoxolan-2-yl]-2-octadecanoyloxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-RYNSOKOISA-N 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 239000008406 cosmetic ingredient Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- UTZNELIJGYWMKS-UHFFFAOYSA-N phenylmethanol;hydrate Chemical compound O.OCC1=CC=CC=C1 UTZNELIJGYWMKS-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- -1 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000001589 sorbitan tristearate Substances 0.000 description 1
- 235000011078 sorbitan tristearate Nutrition 0.000 description 1
- 229960004129 sorbitan tristearate Drugs 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Saccharide Compounds (AREA)
- Cosmetics (AREA)
- Grain Derivatives (AREA)
- Fats And Perfumes (AREA)
- Confectionery (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An elegant topical cream composition in the form of a water-in-oil emulsion, containing betamethasone dipropionate, for the treatment of inflammation.
Description
8 0 4 2 PATENTS ACT 1964 c COMPLETE SPECIFICATION "IMPROVED BETAMETHASONE DIPROPIONATE CREAM" APPLICATION Hajfo SPECIRCATIOM F!L2D U -fV ♦ SCHERING CORPORATION, a corporation organised and existing under the laws of the State of New Jersey, United States of America, of Galloping Hill Road, Kenilworth, New Jersey 07033, United States of America. - 1 - 5 S042 Case 2323 - la - IMPROVED BETAMETHASONE DIPROPIONATE CREAM This invention relates to a cream formulation of betamethasone dipropionate having improved properties. 5 U.S. Patent No. 4,070,462 discloses a steroid ointment having very good efficacy. The effectiveness of this composition is believed to be due to the complete dissolution of the steroid in the ointment. However, this ointment, like others, feels somewhat 10 greasy when applied to the skin. Another product currently on the market (Diprosone Cream) is an oil-in-water emulsion containing, in addition to betamethasone dipropionate, water, mineral oil, white petrolatum, ceteth 20, cetostearyl alcohol, monobasic sodium 15 phosphate, and phosphoric acid, preserved with 4- chloro-m-cresol and propylene glycol. Although this formula is cosmetically more elegant than the previously discussed ointment, it is not as effective.
European Patent Application No. 84105109.7 20 filed May 5, 1984 (published November 21, 1984 under the number 125594) discloses a cream-like composition having better efficacy than Diprosone Cream. -2- The present invention provides a betamethasone dipropionate cream formulation having cosmetic elegance and, very surprisingly/ efficacy similar to the ointment of U.S. Patent No. 4,070,462. 5 This is particularly unexpected in view of the fact that the present invention is in the form of a water-in-oil emulsion, throughout which the steroid is ^ dispersed, i.e., the steroid is not completely dissolved. Furthermore, the composition are 10 surprisingly stable for water-in-oil emulsions.
Some steroidal ointments have a tendency to suppress the hypopituitary adrenal (HPA) axis, causing a potentially dangerous decrease in the level of Cortisol in the blood. The present compositions show 15 little, if any, tendency to cause HPA-axis suppression.
The present invention comprises an esthetically elegant topical composition for the treatment of inflammation in the form of a water-in-oil emulsion comprising by weight based on the total weight 20 of the composition: (a) 0.02 to 0.1 percent betamethasone dipropionate, (b) 15 to 40 percent petrolatum (preferably 20 to 30 percent), * 25 (c) 3 to 15 percent beeswax (preferably 7 to 12 percent), (d) 3.5 to 17.5 percent sorbitol (preferably 7 to 14 percent), dissolved in the water present, (e) 2.5 to 15 percent propylene glycol 30 (preferably 3 to 8 percent) (f) buffer to maintain the pH of the composition within the range of 3 to 6, -3- (g) sufficient amounts of at least one hydrophilic emulsifier and at least one lipophilic emulsifier to stabilize the emulsion and disperse the betamethasone dipropionate, wherein the HLB of the 5 emulsifiers is within the range of 2 to 8 (preferably 4 to 6), (h) sufficient dermatologically acceptable preservative to prevent degradation of the composition by microorganisms, and 10 (i) water.
Preferably the formulations contain from 3 to 15 percent cyclomethicone (more preferably 5 to 10 percent). The preferred buffer system comprises 0.3 percent monobasic sodium phosphate monohydrate and 15 0.001 percent phosphoric acid. Other buffer systems, for example a combination of citric acid monohydrate and trisodium citrate dihydrate or succinic acid and sodium hydroxide, may be used.
The preferred hydrophilic emulsifier is 2 0 ceteth 20, in the amount of 0.01 to 2 percent, preferably 0.3 to 0.7 percent. Other hydrophilic emulsifiers for use in the compositions include polyoxyethylene sorbitan mono-oleate, poiyoxyethylene monostearate, polyoxyethylene lauryl ether, and 25 polysorbate 60 and combinations thereof.
The preferred lipophilic emulsifier is glyceryl oleate in the amount of 1 to 5 percent, preferably 2 to 4 percent. Other acceptable lipophilic emulsifiers include sorbitan tristearate, glyceryl 30 stearate, propylene glycol stearate, sorbitan sesquioleate and combinations thereof.
The HLB is defined by Griffin, W.C., J. Soc. Cosmetic Chemist, 1, 311 id="p-1949" id="p-1949" id="p-1949" id="p-1949"
id="p-1949"
[1949] and 5, 249 id="p-1954" id="p-1954" id="p-1954" id="p-1954"
id="p-1954"
[1954]. The HLB reflects the balance between hydrophilic and lipophilic strength of the emulsifiers. The higher HLB indicates a stronger hydrophilic tendency of the emulsification system.
The preferred preservative is 0.03 to 0.2 percent 4-chloro-m-cresol (preferably 0.07 to 0.12 percent). Other acceptable preservatives include benzyl alcohol, sorbic acid, methyl ja-hydroxybenzoate, propyl jv-hydroxybenzoate, and combinations thereof.
The petrolatum can be white or yellow petrolatum and the beeswax can be white or yellow wax. However, for the sake of providing a white cream, these are preferably used as white petrolatum and white wax.
All percentages are by weight. The definitions of components whose chemical composition is not immediately clear from the name used, such as "ceteth 20", may be found in the CTFA Cosmetic Ingredients Dictionary, 3rd Edition, published by the Cosmetic, Toiletry, and Fragrance Association, Inc., Washington, D.C.
In the preparation of the compositions according to the invention, the sorbitol is conveniently mixed in as an aqueous solution, e.g. as a 70% solution of sorbitol in water. -5- EXAMPLE 1 Quantity, mg/g Ingredient of Emulsion betamethasone dipropionate 0.64 5 white petrolatum, USP 250 white wax flakes, NF 100 cyclomethicone 70 glyceryl oleate 30 ceteth 20 0.5 10 70% solution of sorbitol 150 in water 4-chloro-m-cresol 1 propylene glycol 50 monobasic sodium phosphate 2,65 15 monohydrate phosphoric acid, NF 0.01 purified water, USP q.s. ad 1 g.
PROCEDURE 1. Heat about 80 percent of the water to 20 70°C. Dissolve the monobasic sodium phosphate monohydrate, 4-chloro-m-cresol, and propylene glycol in the heated water. Adjust the pH to 4.5 with a 1 percent solution of phosphoric acid in water. 2. To a separate vessel charge the white 25 petrolatum, white wax flakes, and glyceryl oleate/propylene glycol mixture. Melt and heat to 75°C with agitation. Charge the sorbitol solution and cyclomethicone while maintaining 70°C. 3. Combine the mixtures resulting from steps 30 1 an'i 2 with rapid agitation and cool the combination to 350C with medium agitation. 4. Heat the remaining portion of the water to *'«*C in a separate vessel and dissolve the ceteth 20 ther-i". Cool to 35°C. -6- 5. To about 90 percent of the solution of step 4, charge the betamethasone dipropionate and mill until a uniform dispersion is obtained. 6. Add the milled dispersion from step 5 and the remainder of the ceteth-water mixture from step 4 to the combination of step 3. Mix at 35°C until uniform. Cool the batch to room temperature with slow agitation.
EXAMPLE 2 10 15 20 Ingredient betamethasone dipropionate white petrolatum USP white wax flakes NF cyclomethicone glyceryl oleate ceteth 20 70% solution of sorbitol in water 4-chloro-m-cresol propylene glycol citric acid monohydrate trisodium citrate dihydrate purified water USP Quantity, mg/g of Emulsion 0.64 300 70 50 30 0.5 150 1 50 0.7 1.9 q.s. ad 1 g. 25 The ingredients are combined in a manner similar to that of example 1. -7- EXAMPLE 3 10 15 Ingredient betamethasone dipropionate white petrolatum USP white wax flakes NF cyclomethicone glyceryl oleate ceteth 20 70% solution of sorbitol in water benzyl alcohol propylene glycol monobasic sodium phosphate monohydrate phosphoric acid NF purified water USP Quantity, mg/g of Emulsion 0.64 200 100 100 30 0.5 150 10 50 2.65 0.01 q. s. ad 1 g .
The ingredients are combined in a manner similar to that of example 1. 4 -8- EXAMPLE 4 Quantity, mg/g Ingredient of Emulsion betamethasone dipropionate 0.64 5 white petrolatum USP 300 white wax flakes NF 50 cyclomethicone 50 sorbitan sesquioleate 40 polysorbate 60 10 10 70% solution of sorbitol 100 in water 4-chloro-m-cresol 1 propylene glycol 50 monobasic sodium phosphate 2.65 15 monohydrate phosphoric acid NF 0.01 purified water USP q.s. ad 1 g.
The ingredients are combined in a manner similar to that of example 1. 20 When applied to the skin, the formulations of the examples are found to be equivalent to the ointment of U.S. Patent No. 4,070,462, in vasoconstrictor and anti-inflammatory activity, despite their being in the r form of an elegant cream rather than an ointment. 25 Furthermore, formulations of the present invention have j little or no tendency to suppress the HPA axis. -9-
Claims (8)
1. An elegant topical water-in-oil composition for the treatment of inflammation comprising by weight based on the total weight of the 5 composition: (a) 0.02 to 0.1 percent betamethasone dipropionate, (b) 15 to 40 percent petrolatum, (c) 3 to 15 percent beeswax, 10 (d) 3.5 to 17.5 percent sorbitol, dissolved in the water present, (e) 2.5 to 15 percent propylene glycol, (f) buffer to maintain the pH of the composition within the range of 3 to 6, 15 (g) sufficient amounts of at least one hydrophilic emulsifier and at least one lipophilic emulsifier to stabilize the emulsion and disperse the betamethasone dipropionate, wherein the HLB of the emulsifiers is within the range of 2 to 8, 20 (h) sufficient dermatologically acceptable preservative to prevent degradation of the composition by microorganisms, and (i) water.
2. A composition as claimed in claim 1 25 wherein the petrolatum is white petrolatum and the beeswax is white wax.
3. A composition as claimed in claim 2 wherein: the amount of white petrolatum is 20 to 30 percent, the amount of white wax is 7 to 12 percent, 30 the amount of sorbitol is 7 to 14 percent, the amount of propylene glycol is 3 to 8 percent, and the HLB of the emulsifiers is within the range of 4 to 6. -10-
4. A composition as claimed in any of claims 1 to 3 further comprising: (j) 3 to 15 percent cyclomethicone.
5. A composition as claimed in claim 4 5 comprising approximately: (a) 0.06 percent betamethasone dipropionate, (b) 25 percent white petrolatum, (c) 10 percent white wax, 10 (d) 10.5 percent sorbitol, (e) 5 percent propylene glycol, (f) 0.3 percent monobasic sodium phosphate monohydrate and 0.001 percent phosphoric acid, 15 (g) 0.05 percent ceteth 20 and 3 percent glycerol oleate, (h) 0.1 percent 4-chloro-m-cresol, (i) water, and (j) 7 percent cyclomethicone. 20
6. A composition as claimed in claim 4 comprising approximately: (a) 0.06 percent betamethasone dipropionate, (b) 30 percent white petrolatum, 25 (c) 7 percent white wax, (d) 10.5 percent sorbitol, (e) 5 percent propylene glycol, (f) 0.07 percent citric acid monohydrate and 0.2 percent trisodium citrate dihydrate, -11- (g) 0.05 percent ceteth 20 and 3 percent glyceryl oleate, (h) 0.1 percent 4-chloro-m-cresol, (i) water, and 5 (j) 5 percent cyclomethicone.
7. A composition as claimed in claim 4 comprising approximately: (a) 0.06 percent betamethasone dipropionate, 10 (b) 20 percent white petrolatum, (c) 10 percent white wax, (d) 10.5 percent sorbitol, (e) 5 percent propylene glycol, (f) 0.001 phosphoric acid and 0.3 15 percent monobasic sodium phosphate monohydrate, (g) 0.05 percent ceteth 20 and 3 percent glycerol oleate, (h) 1 percent benzyl alcohol, (i) water, and 20 (j) 10 percent cyclomethicone.
8. A composition as claimed in claim 4 comprising approximately: (a) 0.06 percent betamethasone dipropionate, 25 (b) 30 percent white petrolatum, (c) 5 percent white wax, (d) 7 percent sorbitol, (e) 5 percent propylene glycol, (f) 0.001 percent phosphoric acid and 30 0.3 percent monobasic sodium phosphate m>«ohydrate, -12- (g) 1 percent polysorbate 60 and 4 percent sorbitan sesquioleate, (h) 0.1 percent 4-chloro-m-cresol, (i) water, and (j) 5 percent cyclomethicone. Dated this 23rd day of November 1984. BY: TOMKIHS & CO,, 5, Dartmouth Road, Dublin 6.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US06/559,671 US4489071A (en) | 1983-12-09 | 1983-12-09 | Betamethasone dipropionate cream |
Publications (2)
Publication Number | Publication Date |
---|---|
IE843002L true IE843002L (en) | 1985-06-09 |
IE58042B1 IE58042B1 (en) | 1993-06-16 |
Family
ID=24234538
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE300284A IE58042B1 (en) | 1983-12-09 | 1984-11-23 | Improved betamethasone dipropionate cream |
Country Status (15)
Country | Link |
---|---|
US (1) | US4489071A (en) |
EP (1) | EP0146065B1 (en) |
AT (1) | ATE44462T1 (en) |
AU (1) | AU565947B2 (en) |
CA (1) | CA1238276A (en) |
DE (1) | DE3478899D1 (en) |
DK (1) | DK164022C (en) |
GR (1) | GR81129B (en) |
HK (1) | HK42292A (en) |
IE (1) | IE58042B1 (en) |
IL (1) | IL73626A (en) |
MY (1) | MY100049A (en) |
NZ (1) | NZ210356A (en) |
SG (1) | SG38892G (en) |
ZA (1) | ZA849231B (en) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3534742A1 (en) * | 1985-09-28 | 1987-04-09 | Beiersdorf Ag | HYDROCORTISON'S MOST CONTAINING W / O CREAM |
US4808610A (en) * | 1986-10-02 | 1989-02-28 | Schering Corporation | Mometasone furoate anti-inflammatory cream composition using hexylene glycol |
US4775529A (en) * | 1987-05-21 | 1988-10-04 | Schering Corporation | Steroid lotion |
US5332577A (en) * | 1988-12-27 | 1994-07-26 | Dermamed | Transdermal administration to humans and animals |
US5241925A (en) * | 1988-12-27 | 1993-09-07 | Dermamed | Apparatus and techniques for administering veterinary medicaments |
US5324521A (en) * | 1989-12-18 | 1994-06-28 | Dermamed | Systems for transdermal administration of medicaments |
US5512278A (en) * | 1994-01-11 | 1996-04-30 | Phylomed Corporation | Ointment base useful for pharmaceutical preparations |
US7544674B2 (en) * | 2002-10-25 | 2009-06-09 | Galderma S.A. | Topical skin care composition |
CN101167730B (en) * | 2007-10-24 | 2010-11-24 | 严洁 | Compound betamethasone suspension injection |
FR3039399B1 (en) * | 2015-07-31 | 2018-08-24 | Idl International Drug Licensing | CREAM FOR THE ADMINISTRATION OF STEROIDS AND PROCESS FOR PREPARING THE SAME |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4070462A (en) * | 1976-10-26 | 1978-01-24 | Schering Corporation | Steroid ointment |
US4346086A (en) * | 1981-06-09 | 1982-08-24 | Beiersdorf Aktiengesellschaft | Corticosteroid-containing cream |
DE3483051D1 (en) * | 1983-01-26 | 1990-10-04 | Procter & Gamble | COSMETIC PENS. |
-
1983
- 1983-12-09 US US06/559,671 patent/US4489071A/en not_active Expired - Lifetime
-
1984
- 1984-11-23 IE IE300284A patent/IE58042B1/en not_active IP Right Cessation
- 1984-11-26 ZA ZA849231A patent/ZA849231B/en unknown
- 1984-11-26 IL IL73626A patent/IL73626A/en not_active IP Right Cessation
- 1984-11-27 NZ NZ210356A patent/NZ210356A/en unknown
- 1984-11-28 AU AU35980/84A patent/AU565947B2/en not_active Expired
- 1984-11-30 GR GR81129A patent/GR81129B/en unknown
- 1984-12-01 AT AT84114635T patent/ATE44462T1/en not_active IP Right Cessation
- 1984-12-01 EP EP84114635A patent/EP0146065B1/en not_active Expired
- 1984-12-01 DE DE8484114635T patent/DE3478899D1/en not_active Expired
- 1984-12-06 DK DK582284A patent/DK164022C/en not_active IP Right Cessation
- 1984-12-07 CA CA000469648A patent/CA1238276A/en not_active Expired
-
1987
- 1987-07-14 MY MYPI87001013A patent/MY100049A/en unknown
-
1992
- 1992-04-07 SG SG38892A patent/SG38892G/en unknown
- 1992-06-11 HK HK422/92A patent/HK42292A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
EP0146065A3 (en) | 1985-08-07 |
IL73626A (en) | 1987-12-31 |
ATE44462T1 (en) | 1989-07-15 |
CA1238276A (en) | 1988-06-21 |
ZA849231B (en) | 1985-07-31 |
EP0146065B1 (en) | 1989-07-12 |
DK582284A (en) | 1985-06-10 |
DK582284D0 (en) | 1984-12-06 |
HK42292A (en) | 1992-06-19 |
AU565947B2 (en) | 1987-10-01 |
IE58042B1 (en) | 1993-06-16 |
US4489071A (en) | 1984-12-18 |
NZ210356A (en) | 1987-04-30 |
MY100049A (en) | 1989-06-29 |
DK164022C (en) | 1992-09-28 |
EP0146065A2 (en) | 1985-06-26 |
DK164022B (en) | 1992-05-04 |
DE3478899D1 (en) | 1989-08-17 |
IL73626A0 (en) | 1985-02-28 |
GR81129B (en) | 1985-04-01 |
SG38892G (en) | 1992-05-22 |
AU3598084A (en) | 1985-06-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5422361A (en) | Stable cream and lotion bases for lipophilic drug compositions | |
US4808610A (en) | Mometasone furoate anti-inflammatory cream composition using hexylene glycol | |
AU692486B2 (en) | Pharmaceutical or veterinary composition comprising mupirocin or a salt thereof in a cream base | |
US4333927A (en) | Skin preparation | |
EP0146065B1 (en) | Improved betamethasone dipropionate cream | |
JPH0395120A (en) | Spironolactone composition for local use | |
JPS58225009A (en) | Pharmaceutical preparation of corticosteroid for external use | |
WO1992014472A1 (en) | Compositions for topical administration containing fluticasone propionate and oxiconazole or its salts | |
EP1660029B1 (en) | Use of pentylene glycol as solvent for hydrocortisone or derivatives thereof | |
DE69919597T2 (en) | TOPICAL FORMULATIONS CONTAINING SKIN PENETRATION AGENTS, AND ITS USE | |
US4299828A (en) | Corticosteroid stick formulations | |
EP0325949B1 (en) | Concentrated solutions of corticosteroids and method of making them | |
CA1155394A (en) | Corticosteroid stick formulations | |
GB2068227A (en) | Topical ointment | |
WO2004105686A2 (en) | Novel topical steroid cream formulations | |
JPH10182458A (en) | Indomethacin-containing preparation composition for external use | |
RU2148998C1 (en) | Pharmaceutical or veterinary composition (variants) and method of composition preparing | |
US20030130248A1 (en) | Topical anti-inflammatory compositions | |
JPH07285852A (en) | Nonaqueous oily ointment base and ointment for skin external use |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MK9A | Patent expired |